The overall objective of this project is to delineate structural events at the cellular level in intestinal antigen processing and luminal antigen clearance. M cells in Peyer's patches take up soluble and particulate antigen, then transport it to lymphocytes in the epithelium. Using ultrastructural autoradiography and immunoperoxidase labeling, we will determine where M cells originate, how long they survive and whether the lymphocytes receiving antigen in their interstices are T cells or B cells. Because lysosomes are the rate-limiting factor in epithelial degradation of macromolecules, we will determine quantitatively whether there is a relative deficit in M cell lysosomes. We will study the impact of cortisone and immunization on transport by M cells using ferritin as the model antigen. Giardia, which can penetrate the epithelial barrier, initiate an intraluminal cellular immune response through an M cell independent process. Macrophage role in initiating this M cell independent immune response will be studied in vivo by destroying macrophages with carrageenan. Attachment of sensitized and unsensitized macrophages to Giardia will be studied in vitro. During immune clearance we found that lymphocytes enter the lumen and attach to Giardia. We will determine if these are T cells by examining genetically and surgically T deficient mice prospectively infected with Giardia.